NG2/CSPG4 attenuates motility in mandibular fibrochondrocytes under serum starvation conditions.

The migration of mandibular fibrochondrocytes is important for the development of the mandible, the homeostasis of the mandibular cartilage, and for the capacity of the tissue to respond to injury. Mandibular fibrochondrocytes have to overcome formidable obstacles during migration including a dense and heterogeneous three-dimensional matrix. Guiding the direction of cell migration and commitment to a migratory phenotype in this microenvironment necessitates a multivalent response to chemotactic and extracellular matrix-mediated stimuli. One of the key matrix components in the cartilage of the temporomandibular joint is type VI collagen. Neuron/glial antigen 2 (NG2/CSPG4) is a transmembrane proteoglycan that binds with collagen VI and has been implicated in a wide range of cell behaviors including cell migration, motility, adhesion, and proliferation. While NG2/CSPG4 has been shown to be a key regulator of mandibular cartilage homeostasis, its role in the migration of mandibular fibrochondrocytes during normal and cell stress conditions has yet to be resolved. Here, we address this gap in knowledge by characterizing NG2/CSPG4-dependent migration in mandibular fibrochondrocytes using primary mandibular fibrochondrocytes isolated from control and full length NG2/CSPG4 knockout mice, in primary mandibular fibrochondrocytes isolated from NG2|DsRed reporter mice and in an immortalized mandibular fibrochondrocyte cell line with a mutated NG2/CSPG4 ectodomain. All three cells demonstrate similar results, with loss of the full length or truncated NG2/CSPG4 increasing the rate of cell migration in serum starvation/cell stress conditions. These findings clearly implicate NG2/CSPG4 as a key molecule in the regulation of cell migration in mandibular fibrochondrocytes in normal and cell stress conditions, underscoring the role of NG2/CSPG4 as a mechanosensitive signaling hub in the mandibular cartilage.

The role of complement C5a receptor in DPSC odontoblastic differentiation and in vivo reparative dentin formation.

Therapeutic dentin regeneration remains difficult to achieve, and a majority of the attention has been given to anabolic strategies to promote dentinogenesis directly, whereas, the available literature is insufficient to understand the role of inflammation and inflammatory complement system on dentinogenesis. The aim of this study is to determine the role of complement C5a receptor (C5aR) in regulating dental pulp stem cells (DPSCs) differentiation and in vivo dentin regeneration. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with the C5aR agonist and C5aR antagonist. In vivo dentin formation was evaluated using the dentin injury/pulp-capping model of the C5a-deficient and wild-type mice. In vitro results demonstrate that C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP, while the C5aR activation increased these key odontogenic genes compared to control. A reparative dentin formation using the C5a-deficient mice shows that dentin regeneration is significantly reduced in the C5a-deficient mice. These data suggest a positive role of C5aR in the odontogenic DPSCs differentiation and tertiary/reparative dentin formation. This study addresses a novel regulatory pathway and a therapeutic approach for improving the efficiency of dentin regeneration in affected teeth.

NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis.

Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen, and has been implicated in the cell stress response through mechanical loading-sensitive signaling networks including ERK 1/2. The objective of this study is to define the role of NG2/CSPG4 in the initiation and progression of TMJ OA and to determine if NG2/CSPG4 engages ERK 1/2 in a mechanical loading dependent manner. In vivo, we induced TMJ OA in control and NG2/CSPG4 knockout mice using a surgical destabilization approach. In control mice, NG2/CSPG4 is depleted during the early stages of TMJ OA and NG2/CSPG4 knockout mice have more severe cartilage degeneration, elevated expression of key OA proteases, and suppression of OA matrix synthesis genes. In vitro, we characterized the transcriptome and protein from control and NG2/CSPG4 knockout cells and found significant dysregulation of the ERK 1/2 signaling axis. To characterize the mechanobiological response of NG2/CSPG4, we applied mechanical loads on cell-agarose-collagen scaffolds using a compression bioreactor and illustrate that NG2/CSPG4 knockout cells fail to mechanically activate ERK 1/2 and are associated with changes in the expression of the same key OA biomarkers measured in vivo. Together, these findings implicate NG2/CSPG4 in the mechanical homeostasis of TMJ cartilage and in the progression of degenerative arthropathies including OA.

Mechanical Loading Disrupts Focal Adhesion Kinase Activation in Mandibular Fibrochondrocytes During Murine Temporomandibular Joint Osteoarthritis.

PURPOSE: Mechanical overloading is a key initiating condition for temporomandibular joint (TMJ) osteoarthritis (OA). The integrin-focal adhesion kinase (FAK) signaling axis is implicated in the mechanobiological response of cells through phosphorylation at Tyr397 (pFAK) but poorly defined in TMJ health and disease. We hypothesize that mechanical overloading disrupts TMJ homeostasis through dysregulation of FAK signaling. MATERIALS AND METHODS: To assess if FAK and pFAK are viable clinical targets for TMJ OA, peri-articular tissues were collected from patients with TMJ OA receiving a total TMJ replacement. To compare clinical samples with preclinical in vivo studies of TMJ OA, the joints of c57/bl6 mice were surgically destabilized and treated with and without inhibitor of pFAK (iFAK). FAK signaling and TMJ OA progression was evaluated and compared using RT-PCR, western blot, immunohistochemistry, and histomorphometry. To evaluate mechanical overloading in vitro, primary murine mandibular fibrochondrocytes were seeded in a 4% agarose-collagen scaffold and loaded in a compression bioreactor with and without iFAK. RESULTS: FAK/pFAK was mostly absent from the articular cartilage layer in the clinical sample and suppressed on the central condyle and elevated on the lateral and medial condyle in murine TMJ OA. In vitro, compressive loading lowered FAK/pFAK levels and elevated the expression of TGFß, NG2, and MMP-13. iFAK treatment suppressed MMP13 and Col6 and elevated TGFß, NG2, and ACAN in a load independent manner. In vivo, iFAK treatment moderately attenuated OA progression and increased collagen maturation. CONCLUSION: These data illustrate that FAK/pFAK is implicated in the signaled dysfunction of excessive mechanical loading during TMJ OA and that iFAK treatment can moderately attenuate the progression of cartilage degeneration in the mandibular condyle.

Two-photon fluorescence and second harmonic generation characterization of extracellular matrix remodeling in post-injury murine temporomandibular joint osteoarthritis.

End stage temporomandibular joint osteoarthritis (TMJ-OA) is characterized by fibrillations, fissures, clefts, and erosion of the mandibular condylar cartilage. The goal of this study was to define changes in pericellular and interterritorial delineations of the extracellular matrix (ECM) that occur preceding and concurrent with the development of this end stage degeneration in a murine surgical instability model. Two-photon fluorescence (TPF) and second harmonic generation (SHG) microscopy was used to evaluate TMJ-OA mediated changes in the ECM. We illustrate that TPF/SHG microscopy reconstructs the three-dimensional network of key fibrillar and micro-fibrillar collagens altered during the progression of TMJ-OA. This method not only generates spatially distinct pericellular and interterritorial delineations of the ECM but distinguishes early and end stage TMJ-OA by signal organization, orientation, and composition. Early stage TMJ-OA at 4- and 8-weeks post-injury is characterized by two structurally distinct regions containing dense, large fiber collagens and superficial, small fiber collagens rich in types I, III, and VI collagen oriented along the mesiodistal axis of the condyle. At 8-weeks post-injury, type VI collagen is locally diminished on the central and medial condyle, but the type I/III rich superficial layer is still present. Twelve- and 16-weeks post-injury mandibular cartilage is characteristic of end-stage disease, with hypocellularity and fibrillations, fissures, and clefts in the articular layer that propagate along the mediolateral axis of the MCC. We hypothesize that the localized depletion of interterritorial and pericellular type VI collagen may signify an early marker for the transition from early to end stage TMJ-OA, influence the injury response of the tissue, and underlie patterns of degeneration that follow attritional modes of failure.

Particle-Attachment-Mediated and Matrix/Lattice-Guided Enamel Apatite Crystal Growth.

Tooth enamel is a hard yet resilient biomaterial that derives its unique mechanical properties from decussating bundles of apatite crystals. To understand enamel crystal nucleation and growth at a nanoscale level and to minimize preparation artifacts, the developing mouse enamel matrix was imaged in situ using graphene liquid cells and atomic resolution scanning transmission electron and cryo-fracture electron microscopy. We report that 1-2 nm diameter mineral precipitates aggregated to form larger 5 nm particle assemblies within ameloblast secretory vesicles or annular organic matrix subunits. Further evidence for the fusion of 1-2 nm mineral precipitates into 5 nm mineral aggregates via particle attachment was provided by matrix-mediated calcium phosphate crystal growth studies. As a next step, aggregated particles organized into rows of 3-10 subunits and developed lattice suprastructures with 0.34 nm gridline spacings corresponding to the (002) planes of apatite crystals. Mineral lattice suprastructures superseded closely matched organic matrix patterns, suggestive of a combination of organic/inorganic templates guiding apatite crystal growth. Upon assembly of 2-5 nm subunits into crystal ribbons, lattice fringes indicative of the presence of larger ordered crystallites were observed surrounding elongating crystal ribbons, presumably guiding the c-axis growth of composite apatite crystals. Cryo-fracture micrographs revealed reticular networks of an organic matrix on the surface of elongating enamel crystal ribbons, suggesting that protein coats facilitate c-axis apatite crystal growth. Together, these data demonstrate (i) the involvement of particle attachment in enamel crystal nucleation, (ii) a combination of matrix- and lattice-guided crystal growth, and (iii) fusion of individual crystals via a mechanism similar to Ostwald ripening.

Neuron/Glial Antigen 2-Type VI Collagen Interactions During Murine Temporomandibular Joint Osteoarthritis.

The degeneration of articular cartilage underscores the clinical pathology of temporomandibular joint osteoarthritis (TMJ-OA) and is promoted through dysfunctional biochemical or biophysical signaling. Transduction of these signals has a multifaceted regulation that includes important cell-matrix derived interactions. The matrix encapsulating the cells of the mandibular condylar cartilage (MCC) is rich in type VI collagen. Neuron/glia antigen 2 (NG2) is a type I transmembrane proteoglycan that binds with type VI collagen. This study defines the temporospatial dynamics of NG2-type VI collagen interactions during the progression of TMJ-OA. Membrane-bound NG2 is found to colocalize with pericellular type VI collagen in superficial layer cells in the MCC perichondrium but is present at high levels in the cytosol of chondroblastic and hypertrophic cells. When TMJ -OA is induced using a surgical instability model, localized disruptions of pericellular type VI collagen are observed on the central and medial MCC and are associated with significantly higher levels of cytosolic NG2. NG2 localized within the cytosol is found to be transported through clathrin and dynamin mediated endocytic pathways. These findings are consistent with NG2 behavior in other injury models and underscore the potential of NG2 as an entirely novel molecular mechanism of chondrocyte function contextually linked with TMJ-OA.

In vivo bone strain in the mandibular corpus of Sapajus during a range of oral food processing behaviors.

It has been hypothesized that mandibular corpus morphology of primates is related to the material properties of the foods that they chew. However, chewing foods with different material properties is accompanied by low levels of variation in mandibular strain patterns in macaques. We hypothesized that if variation in primate mandible form reflects adaptations to feeding on foods with different material and geometric properties, then this variation will be driven primarily by differences in oral food processing behavior rather than differences in chewing per se. To test this hypothesis, we recorded in vivo bone strain data from the lateral and medial surfaces of the mandibular corpus during complete feeding sequences in three adult male Sapajus as they fed on foods with a range of sizes and material properties. We assessed whether variation in mandibular corpus strain regimes is associated with variation in feeding behaviors and/or chewing on different foods, and we quantified the relative variation in mandibular corpus strain regimes associated with chewing on foods of different material properties versus a range of oral food processing behaviors (incisor, premolar, and molar biting; pulling on incisors; mastication). Feeding behavior had a significant effect on mandibular corpus strain regimes, as did chewing side and the cycle number in a feeding sequence. However, food type had weaker effects and usually only through interaction effects with chewing side and/or cycle type. Strain regimes varied most across different chew sides, then across different behaviors, and lastly between mastication cycles on different foods. Strain magnitudes associated with premolar, molar, and incisor biting were larger than those recorded during mastication. These data suggest that intra- and inter-specific variation in mandible morphology is a trade-off between performance requirements of different oral food processing behaviors and of variation in chewing side, with direct effects of food type being less important.

Varanoid Tooth Eruption and Implantation Modes in a Late Cretaceous Mosasaur.

Erupting teeth are some of the oldest witnesses of developmental processes in the vertebrate fossil record and provide an important resource for vertebrate cladistics. Here, we have examined a mosasaur jaw fragment from central Texas using ultrathin ground section histology and 3D tomographic imaging to assess features critical for the cladistic placement of mosasaurs among varanoids vs. snakes: (i) the orientation of replacement teeth compared to the major tooth axis, (ii) the occurrence of resorption pits, and (iii) the mode of tooth implantation/attachment to the tooth bearing element (TBE). The replacement tooth studied here developed in an inclined position slightly distal of the deciduous parent tooth, similar to another varanoid squamate, the Gila monster Heloderma suspectum. Ground sections and tomographs also demonstrated that the replacement tooth attachment apparatus was entirely intact and that there was no evidence of mechanical deformation. Sections and tomographs further illustrated that the replacement tooth was located within a bony crypt and the inclination of the crypt matched the inclination of the replacement tooth. These preparations also revealed the presence of a resorption pit within the boundaries of the deciduous tooth that surrounded the developing replacement tooth. This finding suggests that developing mosasaur teeth developed within the walls of resorption pits similar to varanoid tooth germs and unlike developing snake teeth which are surrounded by fibrous connective tissue integuments. Finally, mosasaurs featured pseudo-thecodont tooth implantation with teeth anchored within a socket of mineralized tissue by means of a mineralized periodontal ligament. Together, these data indicate that the moderate inclination of the erupting mosasaur tooth studied here is neither a result of postmortem displacement nor a character representative of snakes, but rather a shared character between Mosasaurs and other varanoids such as Heloderma. In conjunction with the presence of resorption pits and the evidence for pseudothecodont tooth implantation, the tooth eruption and implantation characters described in the present study either place mosasaurs among the varanoids or suggest convergent evolution mechanisms between both clades, with mosasaurs evolving somewhat independently from a common varanoid ancestor.

Lyophilized platelet-rich fibrin (PRF) promotes craniofacial bone regeneration through Runx2.

Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold±0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold±0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p<0.001) when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

Sources of variance in temporal and spatial aspects of jaw kinematics in two species of primates feeding on foods of different properties.

Chewing kinematics reflects interactions between centrally generated motor signals and peripheral sensory feedback from the constantly changing oral environment. Chewing is a strongly modulated behavior that responds to differences in material properties among different type of foods and to changes in the external physical properties of the food as the bolus gets processed. Feeding, as any complex biological behavior, presents variation at multiple hierarchical levels, from among species or higher-order levels to variation among chewing cycles within a single feeding sequence. Thus, to understand the mechanics and evolution of feeding systems requires estimation of how this variation is distributed across each of these hierarchical levels, which in turn requires large sample sizes. The development of affordable, high-resolution, three-dimensional kinematic recording systems has increased our ability to collect large amounts of data on complete or near-complete feeding sequences that can be used to shed light on the mechanisms of control in vertebrate feeding. In this study, we present data on the nature and sources of variation (from species to chewing cycle levels) in kinematics of chewing in two species of primates, Cebus and Macaca, while they feed on foods of known material properties. Variation in chewing kinematics was not evenly distributed among hierarchical levels. Most of the variation was observed among chewing cycles, most likely in response to changes in the external properties of the food bolus throughout the feeding sequence. Species differences were found in duration and vertical displacement during slow-close phase suggesting that each species exhibits different power stroke dynamics. Cebus exhibited more variable gape cycles than did Macaca, in particular when eating low-toughness foods. This increased ability to temporally and spatially modulate the gape cycle may reflect increased efficiency in processing food because Cebus monkeys use fewer, but longer cycles, than does Macaca when feeding on low-toughness foods. This is due to an increase in duration of the jaw-opening phases of the gape cycle, when the tongue repositions the food bolus in the oral cavity.

The impact of bone and suture material properties on mandibular function in Alligator mississippiensis: testing theoretical phenotypes with finite element analysis.

The functional effects of bone and suture stiffness were considered here using finite element models representing three different theoretical phenotypes of an Alligator mississippiensis mandible. The models were loaded using force estimates derived from muscle architecture in dissected specimens, constrained at the 18th and 19th teeth in the upper jaw and 19th tooth of the lower jaw, as well as at the quadrate-articular joint. Stiffness was varied systematically in each theoretical phenotype. The three theoretical phenotypes included: (i) linear elastic isotropic bone of varying stiffness and no sutures; (ii) linear elastic orthotropic bone of varying stiffness with no sutures; and (iii) linear elastic isotropic bone of a constant stiffness with varying suture stiffness. Variation in the isotropic material properties of bone primarily resulted in changes in the magnitude of principal strain. By comparison, variation in the orthotropic material properties of bone and isotropic material properties of sutures resulted in: a greater number of bricks becoming either more compressive or more tensile, changing between being either dominantly compressive or tensile, and having larger changes in the orientation of maximum principal strain. These data indicate that variation in these model properties resulted in changes to the strain regime of the model, highlighting the importance of using biologically verified material properties when modeling vertebrate bones. When bones were compared within each set, the response of each to changing material properties varied. In two of the 12 bones in the mandible, varied material properties within sutures resulted in a decrease in the magnitude of principal strain in bricks adjacent to the bone/suture interface and decreases in stored elastic energy. The varied response of the mandibular bones to changes in suture stiffness highlights the importance of defining the appropriate functional unit when addressing relationships of performance and morphology.

The influence of food material properties on jaw kinematics in the primate, Cebus.

OBJECTIVE: To quantify the impact of food material properties on temporal and spatial variables of chewing kinematics at the level of the feeding sequence, gape cycle, and gape cycle phases. DESIGN: Three-dimensional kinematics were quantified from two adult, male capuchin monkeys (genus Cebus) while chewing on foods grouped by material properties into two categories, foods of high toughness and foods of low toughness. RESULTS: Total sequence duration and the total number of chews in a sequence are significantly influenced by food material properties, with foods of high toughness having shorter sequence durations and lower total chew numbers per sequence. Mean cycle duration is not impacted by food material properties at the level of the sequence, but food group differences are found when each cycle is compared independently by food group. Prior to chew fifteen, foods of low toughness elicit significantly lower gape cycle durations and significantly lower vertical displacements of M(1). At the level of the chew phase, variance in slow close explains the majority of variance in chew cycle duration prior to chew thirteen, with foods of low toughness eliciting shorter slow close durations and smaller vertical displacements of M(1). The vertical displacement of M(1) throughout the chewing sequence is the primary spatial determinant of variance in the duration of slow close. CONCLUSIONS: These data reveal that chewing behaviour in Cebus is temporally stereotyped at the level of the gape cycle, but temporally and spatially flexible within the cycle, at least partly due to central mechanisms of motor control.

A new scale to measure family members' perception of community health care services for persons with Huntington disease.

UNLABELLED: RATIONALE, AIMS, AND OBJECTIVES: Huntington disease (HD) is a progressive genetic brain disease leading to disruptive cognitive, behavioural and physical impairments. Persons with the condition and their caregivers need appropriate and accessible health care services to help them manage the disease adequately. The purpose of this study was to evaluate the psychometric properties of a new scale that measures family members' perception of community health care services (CHCS) for persons with HD. METHODS: A methodological design was used to examine the initial reliability and dimensionality of the CHCS scale among 245 family members of persons with a diagnosis of HD. Data analysis consisted of computing Cronbach's alpha coefficients, calculating the 95% confidence interval for alpha and performing item-analysis and exploratory factor analysis. RESULTS: Reliability of the scale based on Cronbach's alpha was 0.83. Factor analysis using principal component analysis and varimax rotation suggested that three interpretable factors underlie the scale. Factor 1, HD knowledge, had alpha = 0.82, eigenvalue of 4.67 and explained 33.42% of the variance; factor 2, HD community resources, had alpha = 0.62, eigenvalue of 1.68 and explained 12.02% of the variance; factor 3, individualized HD management, had alpha = 0.77, eigenvalue of 1.45 and explained 10.39% of the variance. CONCLUSIONS: Findings from this study provide evidence of both construct validity and internal consistency reliability of the CHCS scale. Further psychometric testing of the scale in other samples of family caregivers of persons with HD is warranted.

Ecological consequences of scaling of chew cycle duration and daily feeding time in primates.

Feeding systems and behaviors must evolve to satisfy the metabolic needs of organisms. This includes modifications to feeding systems as body size and metabolic needs change. Using our own data and data from the literature, we examine how size-related changes in metabolic needs are met by size-related changes in daily feeding time, chew cycle duration, volume of food processed per chew, and daily food volume intake in primates. Increases in chew cycle duration with body mass in haplorhine primates are described by a simple power function (cycle time alpha body mass(0.181)). Daily feeding time increases with body mass when analyzed using raw data from the "tips" of the primate phylogenetic tree, but not when using phylogenetically independent contrasts. Whether or not daily feeding time remains constant or increases with body mass, isometry of ingested bite size and the slow rate of increase in chew cycle time with body size combine to allow daily ingested food volume to scale faster than predicted by metabolic rate. This positive allometry of daily ingested food volume may compensate for negative allometry of nutrient concentration in primate foods. Food material properties such as toughness and hardness have little impact on scaling of chew cycle durations, sequence durations, or numbers of chews in a sequence. Size-related changes in food processing abilities appear to accommodate size-related changes in food material properties, and primates may alter ingested bite sizes in order to minimize the impacts of food material properties on temporal variables such as chew cycle duration and chew sequence duration.

Scaling of chew cycle duration in primates.

The biomechanical determinants of the scaling of chew cycle duration are important components of models of primate feeding systems at all levels, from the neuromechanical to the ecological. Chew cycle durations were estimated in 35 species of primates and analyzed in conjunction with data on morphological variables of the feeding system estimating moment of inertia of the mandible and force production capacity of the chewing muscles. Data on scaling of primate chew cycle duration were compared with the predictions of simple pendulum and forced mass-spring system models of the feeding system. The gravity-driven pendulum model best predicts the observed cycle duration scaling but is rejected as biomechanically unrealistic. The forced mass-spring model predicts larger increases in chew cycle duration with size than observed, but provides reasonable predictions of cycle duration scaling. We hypothesize that intrinsic properties of the muscles predict spring-like behavior of the jaw elevator muscles during opening and fast close phases of the jaw cycle and that modulation of stiffness by the central nervous system leads to spring-like properties during the slow close/power stroke phase. Strepsirrhines show no predictable relationship between chew cycle duration and jaw length. Anthropoids have longer chew cycle durations than nonprimate mammals with similar mandible lengths, possibly due to their enlarged symphyses, which increase the moment of inertia of the mandible. Deviations from general scaling trends suggest that both scaling of the jaw muscles and the inertial properties of the mandible are important in determining the scaling of chew cycle duration in primates.

Reversible medetomidine/ketamine anesthesia in captive capuchin monkeys (Cebus apella).

BACKGROUND: Medetomidine, an alpha(2)-adrenergic receptor agonist administered with ketamine, induces sedation/anesthesia in non-human primates in a dose-dependent, species-specific manner. METHODS: Two adult male capuchin monkeys enrolled in a study of kinematics of mastication were administered intramuscular (IM) injections of 150, 200 and 400 microg/kg medetomidine or medetomidine (microg/kg)/ketamine (mg/kg) at 200/2, 150/4. Medetomidine was reversed with atipamezole. Animals were then fed for 9-75 minutes. A second anesthesia reversal episode allowed return to home cage. RESULTS: Medetomidine (150 microg/kg)/ketamine (4 mg/kg) provided anesthesia for handling and restraint within 10 minutes of administration. Atipamezole (750 microg/kg) IM provided reversal sufficient for the animal to eat by 22 minutes or perch by 31 minutes. CONCLUSIONS: Medetomidine/ketamine administered IM in Cebus apella results in rapid, reproducible and safe anesthesia which is reversible with atipamezole. Nausea, vomiting or regurgitation were not observed during anesthesia reversal episodes in either the fasted or fed state.

Email teleconsultations: well formulated clinical referrals reduce the need for clinic consultation.

We examined how well primary-care physicians formulated their clinical referrals when asking for help with patient-related clinical problems using an email-based teleconsultation service. Over 100 family physicians made use of the service. The specialists were medical school faculty members. The service was initiated in May 1996 with 19 specialists and expanded to 34 specialties over the next five years. A total of 1618 patient-related clinical questions were analysed, the outcome for the analysis being whether specialists recommended a clinic consultation. Specialists recommended a clinic consultation in response to 10% of their clinical questions about patients. There was a strong association between how family physicians formulated their clinical questions and whether the specialist recommended a clinic consultation. When the family physicians specified a clinical task (P < 0.001), intervention (P = 0.004) and outcome (P < 0.001) in their questions, specialists were less likely to recommend a clinic consultation. This influence was independent of the amount of clinical information included with the question (P > 0.05). About 5% of the questions that included all three question components resulted in the recommendation for a clinic consultation, compared with nearly 30% of the questions containing none of these components. How family physicians formulate their clinical questions influences whether specialists request a clinic consultation.

Effects of respite care for children with developmental disabilities: evaluation of an intervention for at risk families.

Respite child care programs that provide temporary child care, support, and referral services to families of children with developmental disabilities are thought to be a critical component of formal social support interventions deemed necessary to promote healthy family functioning and prevent child maltreatment. This study describes sociodemographic characteristics, parenting stress levels, foster care placement, and founded child maltreatment rates in families of children with developmental disabilities who were using respite care services in a rural Midwestern state. Comparison of matched pre- and post-test Parenting Stress Index scores indicated significant decreases in Total Stress scores (t=3.27, df=86, p=0.0016), Parent Domain scores (t=3.55, df=86, p=0.0006), and Child Domain scores (t=2.2, df=86, p=0.02) following provision of respite care. Through logistic regression, it was determined that life stress, social support, and service level were significantly related to the occurrence of child maltreatment during enrollment ( p < 0.05). The investigator suggests that public health nurses can enhance their case management strategies when working with the parents of children with developmental disabilities by monitoring for caregiver burnout in addition to ensuring that the child is receiving care appropriate for his or her level of need.

Assessing homeland chemical hazards outside the military gates: industrial hazard threat assessments for department of defense installations.

As part of comprehensive joint medical surveillance measures outlined by the Department of Defense, the US Army Center for Health Promotion and Preventive Medicine (USACHPPM) is beginning to assess environmental health threats to continental US military installations. A common theme in comprehensive joint medical surveillance, in support of Force Health Protection, is the identification and assessment of potential environmental health hazards, and the evaluation and documentation of actual exposures in both a continental US and outside a continental US setting. For the continental US assessments, the USACHPPM has utilized the US Environmental Protection Agency (EPA) database for risk management plans in accordance with Public Law 106-40, and the toxic release inventory database, in a state-of the art geographic information systems based program, termed the Consequence Assessment and Management Tool Set, or CATS, for assessing homeland industrial chemical hazards outside the military gates. As an example, the US EPA toxic release inventory and risk management plans databases are queried to determine the types and locations of industries surrounding a continental US military installation. Contaminants of concern are then ranked with respect to known toxicological and physical hazards, where they are then subject to applicable downwind hazard simulations using applicable meteorological and climatological data sets. The composite downwind hazard areas are mapped in relation to emergency response planning guidelines (ERPG), which were developed by the American Industrial Hygiene Association to assist emergency response personnel planning for catastrophic chemical releases. In addition, other geographic referenced data such as transportation routes, satellite imagery and population data are included in the operational, equipment, and morale risk assessment and management process. These techniques have been developed to assist military medical planners and operations personnel in determining the industrial hazards, vulnerability assessments and health risk assessments to continental United States military installations. These techniques and procedures support the Department of Defense Force Protection measures, which provides awareness of a terrorism threat, appropriate measures to prevent terrorist attacks and mitigate terrorism's effects in the event that preventive measures are ineffective.